Clinical applications of live biotherapeutics: Current trends and future prospects

Live biotherapeutic (LBP) is defined by the FDA as a biological product that: (1) contains live organisms, such as bacteria; (2) applies to the prevention, treatment, or cure of a disease or condition of human beings; and (3) is not a vaccine. Progress in microbiome science and the limitations of antibiotics have necessitated the use of LBPs to complement or replace conventional therapies across multiple medical disciplines. The most important advancement is in the infectious disease domain, where fecal microbiota transplantation validated ecological restoration for recurrent Clostridioides difficile infection and paved the way for the first approved LBPs (REBYOTA® and VOWST™/SER-109). Constructing rational microbial consortia and strain-level strategies aim to induce commensal resilience and prevent the establishment of multidrug-resistant organisms. In oncology, gut microbial composition modulates response to immune checkpoint inhibitors. So, defined microbial consortia and engineered E. coli Nissle are being developed to enhance antitumor immunity and localize payloads. Early studies in animals and humans also support the application of this approach in metabolic disease, allergy, and oral health. Translation from benchside to bedside, however, is fraught with hurdles-variable patient response, manufacturing consistency, safety standards, cost, and ethics-exacerbated by heterogeneous global regulations, underscoring the need for harmonization. Precision microbial consortia, programmable "living medicines," and biohybrid formulations could extend LBPs into broader indications and global health, shifting practice toward an ecological model of therapeutics.